The following terms used herein are defined as follows:
The term “stent” means a frame structure containing openings through its wall, typically cylindrical in shape, intended for implantation into the body. A stent may be self-expanding and/or expanded using applied forces.
As used herein, the terms “covered stent” and “stent-graft” are used interchangeably to mean a stent with a cover on at least a portion of its length. The cover can be on the outer surface, the inner surface, on both surfaces of the stent, or the stent may be embedded within the cover itself. The cover may be porous or non-porous and permeable or non-permeable. Active or inactive agents or fillers can be attached to or incorporated into the cover.
Referring to FIG. 4a, as used in this application, the term “wrinkle” 65a, 65b means a fold in a stent cover 62 that has a larger peak to valley height 64 than a thickness 66 of an adjacent stent strut 68. In the illustrated instance where the cover is mounted within the stent, a wrinkle 65a in a cover 62 on the outer surface of a covered stent 60 may be identified where the cover extends beyond the inner surface of the stent struts 68. A wrinkle 65b can also extend radially inward.
Referring to FIG. 4b, a wrinkle 65a in a cover on the inner surface of a covered stent 60 can extend radially outward. Such an outward-extending wrinkle may be identified where the cover 62 extends beyond the outer surface of the stent struts 68 as shown in FIG. 4b. A wrinkle 65b can also extend radially inward as shown in FIG. 4b 
Wrinkles can be observed with unaided vision or they can be observed and measured under magnification, such as optical microscopy. “Wrinkle-free” means a stent covering that is substantially free of “wrinkles.”
As used herein, the term “expand” has two distinct meanings. When used in the context of describing stents, it refers to the increase in diameter of those devices. When used in the context of ePTFE material, it refers to the stretching (i.e., expansion) process used to render PTFE material stronger and porous.
As used herein, the term “self-expanding” means the attribute of a device that describes that it expands outwardly, such as in a general radial direction, upon removal of a constraining means, thereby increasing in diameter without the aid of an external force. That is, self-expanding devices inherently increase in diameter once a constraining mechanism is removed. Constraining means include, but are not limited to, tubes from which the stent or covered stent device is removed, such as by pushing. Alternatively, a constraining tube or sheath may be disrupted to free the device or the constraining means can be unraveled should it be constructed of a fiber or fibers. External forces, as provided by balloon catheters for example, may be used prior to expansion to help initiate an expansion process, during expansion to facilitate expansion, and/or after stent or covered stent deployment to further expand or otherwise help fully deploy and seat the device.
As used herein, the term “fully deployed” refers to the state of a self-expanding stent after which the constraining means has been removed and the stent, at about 37° C. over the course of 30 seconds, has expanded under its own means without any restriction. A portion or portions of a self-expanding stent may be fully deployed and the remainder of the stent may be not fully deployed.
The phrase, “operating diametric range” refers to the diametric size range over which the stent or stent-graft will be used and typically refers to the inner diameter of the device. Devices are frequently implanted in vessel diameters smaller than that corresponding to the device fully deployed state. This operating range may be the labeled size(s) that appear in the product literature or on the product package or it can encompass a wider range, depending on the use of the device.
As used herein, the term “porous” describes a material that contains small or microscopic openings, or pores. Without limitation, “porous” is inclusive of materials that possess pores that are observable under microscopic examination. “Non-porous” refers to materials that are substantially free of pores. The term “permeable” describes a material through which fluids (liquid and/or gas) can pass. “Impermeable” describes materials that block the passage of fluids. It should be appreciated that a material may be non-porous yet still be permeable to certain substances.
Stents and covered stents have a long history in the treatment of trauma-related injuries and disease, especially in the treatment of vascular disease. Stents can provide a dimensionally stable conduit for blood flow. Stents prevent vessel recoil subsequent to balloon dilatation thereby maintaining maximal blood flow. Covered stents can provide the additional benefits of preventing blood leakage through the wall of the device and inhibiting, if not preventing, tissue growth through the stent into the lumen of the device. Such growth through the interstices of the stent may obviate the intended benefits of the stenting procedure.
In the treatment of carotid arteries and the neurovasculature, coverings trap plaque particles and other potential emboli against the vessel wall thereby preventing them from entering the blood stream and possibly causing a stroke. Coverings on stents are also highly desirable for the treatment of aneurismal vascular disease. The covers may further act as useful substrates for adding fillers or other bioactive agents (such as anticoagulant drugs, antibiotics, growth inhibiting agents, and the like) to enhance device performance.
The stent covers may extend along a portion or portions or along the entire length of the stent. Generally, stent covers should be biocompatible and robust. They can be subjected to cyclic stresses about a non-zero mean pressure. Consequently, it is desirable for them to be fatigue and creep resistant in order to resist the long-term effects of blood pressure. It is also desirable that stent covers be wear-resistant and abrasion-resistant. These attributes are balanced with a desire to provide as thin a cover as possible in order to achieve as small a delivery profile as possible. Covers compromise the flow cross-section of the devices, thereby narrowing the blood flow area of the device, which increases the resistance to flow. While increased flow area is desirable, durability can be critical to the long-term performance of covered stents. Design choice, therefore, may favor the stronger, hence thicker, covering. Thick covers, however, are more resistant to distension than otherwise identical thinner covers.
Some balloon-expandable stent covers are wrinkle-free over the operating range of the stents because the extreme pressures of the balloons can distend the thick, strong covers that are placed onto the stent at a less than a fully deployed stent diameter. Even the thinnest covers in the prior art such as those made of ePTFE (e.g., those taught in U.S. Pat. No. 6,923,827 to Campbell et al., and U.S. Pat. No. 5,800,522 to Campbell et al.), however, may be too unyielding to be distended by the radial forces exerted by even the most robust self-expanding stents.
Non-elastic and non-deformable self-expanding stent covers are, therefore, generally attached in a wrinkle-free state to the stent when the stent is fully deployed. When such covered stents are at any outer diameter smaller than the fully deployed outer diameter, the cover is necessarily wrinkled. These wrinkles, unfortunately, can serve as sites for flow disruption, clot initiation, infection, and other problems. The presence of wrinkles may be especially deleterious at the inlet to covered stents. The gap between the wrinkled leading edge of the cover and the host vessel wall can be a site for thrombus accumulation and proliferation. The adverse consequences of wrinkles are particularly significant in small diameter vessels which are prone to fail due to thrombosis, and even more significant in the small vessels that provide blood to the brain.
The use of thin, strong materials is known for implantable devices (e.g., those taught in U.S. Pat. No. 5,735,892 to Myers et al.). Extremely thin films of expanded PTFE (ePTFE) have been taught to cover both self-expanding and balloon expandable stents. Typically these films are oriented during the construction of the devices to impart strength in the circumferential direction of the device. Consequently, the expanding forces of the self-expanding stents may be far too low to distend these materials. In fact, such devices are generally designed to withstand high pressures. These coverings, like those of other coverings in the art, are wrinkle-free only when the devices are fully deployed.
Thin, extruded but not expanded fluoropolymer tubes have been used to cover self-expanding and balloon-expandable stents (e.g., U.S. Patent Application 2003/0082324 A1 to Sogard). These seamless extruded tube covers are applied to self-expanding stents in the fully deployed state of the stents. The stent coverings, therefore, possess wrinkles upon crushing the device to a diameter smaller than the fully deployed diameter.
Expanded PTFE material has been used to cover stents that are self-expanding up to a given diameter, then use the assistance of a balloon catheter or other expansion force to achieve the desired clinical implantation diameter (e.g., U.S. Pat. No. 6,336,937 to Vonesh et al). Such covers are wrinkled in the range of diameters up to the diameter at which the stent expands on its own. Beyond that diameter, the covers may be relatively wrinkle-free, however, the stent may no longer be freely self-expanding.
Another type of covered stent previously disclosed (e.g., U.S. Patent Application 2002/0178570 A1 to Sogard) is constructed with two polymeric liners laminated together yet not adhered to the stent. In the absence of bonding a liner to the stent, both an inner and outer liner are necessary and they need to be bonded together at the stent openings in order to construct a coherent stent-graft. This construction provides a relatively smooth liner on one side of the stent. The outer liner follows the geometry of the stent strut and is bonded to the inner liner. As such, according to the definition of a “wrinkle” as provided herein, the outer liner is wrinkled. Expanded PTFE liners of self-expanding covered stents made with shape memory alloys were taught to be laminated together at elevated temperatures, as high as 250° C. (and below 327° C.), while not exceeding a stent temperature which might reset the shape memory state of the alloy. In the absence of bonding the liners to the stent struts, gaps are formed between the liners. Such gaps may become filled with biological materials that compromise the blood flow area and, therefore, may restrict blood flow.
Without the addition of other materials, expanded PTFE materials must be heated well above 200° C. in order the heat bond them together. Given that these stent-graft devices are intended to self-expand at body temperature, the temperature at which the alloy may reset is necessarily close to body temperature. This thermal requirement obviates the possibility of heat bonding the liner to the stent at around a 250° C. temperature. Furthermore, the size of the covered stent that can be constructed in this manner is limited by the physics of heat conduction. That is, a 250° C. heat source must be at a suitable distance from the stent during the lamination process. The liners are laminated with the stent at a diameter less than deployed diameter, hence the size of the openings of the stent are smaller than if the liners were laminated at a larger stent diameter. Consequently, small diameter covered stents cannot be made in accordance with these teachings, nor can the liners be bonded to the stent.
U.S. Pat. No. 6,156,064 to Chouinard teaches use of dip coating to apply polymers to self-expanding stents. Stents and stent-grafts are dipped into polymer-solvent solutions to form a film on the stent followed by spray coating and applying a polymeric film to the tube. Stent-grafts comprising at least three layers (i.e., stent, graft, and membrane) are taught to be constructed in this manner.
Stents have also been covered with a continuous layer of elastic material. As taught in U.S. Pat. No. 5,534,287 to Lukic, a covering may be applied to a stent by radially contracting the stent, then placing it inside a tube with a coating on its inner surface. The stent is allowed to expand, thereby bringing it in contact with the coating on the tube. The surface of contact between the stent and the tube is then vulcanized or similarly bonded. No teaching is provided concerning the diameter of the tube relative to the fully deployed stent diameter. The patent specifically teaches in one embodiment the application of the coating on a stent in the expanded condition. The inventor does not teach how to eliminate or even reduce wrinkles in the stent cover. In fact, the patent teaches how to increase the thickness of the coating, a process that would only increase the occurrence of wrinkling. The patent teaches away from the use of a non-elastic material to cover the stent, and specifically teaches away from the use of a “Teflon®” (i.e., PTFE) tube.
U.S. Patent Application 2004/0024448 A1 to Chang et al teaches covered stents with elastomeric materials including PAVE-TFE. Self-expanding stent-grafts made with this material, like those made of other materials in the art, are not wrinkle-free over the operating range of the devices. These coverings of self-expanding stents are typically applied to the stent in the fully-deployed state. Consequently, wrinkles are formed when the stent-graft is crushed to any significant degree.